Control unit for infusion pump units, including a controlled intervention unit

ABSTRACT

A control unit for an electronically controlled pump unit controls the pump unit to infuse insulin into a diabetic&#39;s body in a substantially continuous way according to a preset infusion schedule as a function of time. The control unit includes an intervention unit that continuously evaluates a blood-glucose indicative input for detecting an actual or expected hypoglycaemia and executes, in response to an actual or expected hypoglycaemia, a temporary hypoglycaemia intervention. The intervention includes, for an intervention time interval, overriding the preset infusion schedule by temporarily suspending insulin infusion or temporarily reducing insulin infusion below the preset infusion schedule. The intervention unit adapts its way of operation with respect to executing the hypoglycaemia intervention in accordance with a control signal that is separate from the blood-glucose indicative input. The control unit automatically generates the control signal as a function of time and/or based on sensor input.

RELATED APPLICATIONS

This application is a continuation of PCT/EP2014/071861, filed Oct. 13,2014, which claims priority to EP 13189458.6, filed Oct. 21, 2013, bothof which are hereby incorporated herein by reference in theirentireties.

BACKGROUND

The present disclosure is directed towards diabetes therapy systems asused in the therapy of diabetes mellitus by Continuous SubcutaneousInsulin Infusion (CSII) and control units for a pump unit of suchsystems.

The present disclosure is further directed towards methods forcontrolling operation of an pump unit in such a system.

Continuous Subcutaneous Insulin Infusion (CSII) is an advanced andtherapeutically advantageous way of treating diabetes mellitus. UnderCSII, a diabetic carries a miniaturized infusion pump substantiallycontinuously, night and day. The infusion pump infuses minimalquantities of insulin in a substantially continuous way according to aperson-specific, generally time-variable infusion schedule, thusproviding a so-called basal amount of insulin that is required by thediabetic's body for maintaining a normal or close-to-normal metabolismand in particular glucose concentration. For typical state-of-the-artsystems, the basal administration schedule follows a generally circadiancycle and is preset by a healthcare professional. In addition, insulinpumps are designed to administer larger insulin quantities, so calledboli, within a short period of time on demand, in order to coverdiabetic's food intake, and under exceptional circumstances, such asillness or in case of a hyperglycaemia (also referred to ashyperglycaemic excursion or hyperglycaemic episode), which is asituation of increased glucose concentration, resulting from a relativelack of insulin within the diabetic's body.

Here and following in the present disclosure, “glucose” and phrases like“glucose value” or “glucose concentration” refer to glucose measured ina diabetic's blood, i.e., glucose, or glucose that is correlated withthe glucose, in particular glucose in the subcutaneous tissue orinterstitial fluid.

The opposite to a situation of hyperglycaemia is a hypoglycaemia (alsoreferred to as hypoglycaemic excursion or hypoglycaemic episode), wherethe glucose level is too low, i.e., below a generally desired level,resulting from a relative excess of insulin within the diabetic's body.Both hyperglycaemia and hypoglycaemia may, when not appropriately dealtwith, result in severe and potentially fatal complications. Untreatedhypoglycaemia may in particular lead, within minutes to few hours, tosymptoms and behaviour generally known for and associated withdrunkenness or drug consumption, followed by a hypoglycaemic coma andfinally death. During everyday life, the potential embarrassment thatmay result from hypoglycaemic symptoms is a constant source of concernand causes considerable psychological stress to many diabetics. Insituations where full ability to react, motor capabilities and generalawareness is crucial, like in some sports or when driving a car,hypoglycaemias may lead to potentially fatal accidents. The nocturnalsleep is a serious source of concern for many diabetics because thehypoglycaemia awareness of many diabetics is disabled or largely reducedin this time period.

In order to generally monitor correct operation of the insulin pump andto allow appropriate reaction in case of exceptional circumstances, suchas hyperglycaemic or hypoglycaemic excursions, diabetics on CSII therapyneed to test their glucose level at least several times a day, typicallyusing glucose meters based on invasive (finger-prick) spot measurementsof the glucose and/or, in recent times, using a Continuous GlucoseMonitor (CGM), typically measuring glucose in the interstitial tissue.

While requiring considerable technical effort as well as constantawareness of the diabetic (or a person such as a relative), CSII therapyallows maintaining the diabetic's metabolism and in particular his orher glucose level in a close-to-normal range in everyday life. There is,however, a general concern with respect to the awareness of andappropriate reaction on hypoglycaemias as explained before.

To cope, among others, with such situations, closed-loop-systems (alsoknown as Artificial Pancreas (AP)), have been under development for manyyears now, in which a CGM is operatively coupled to an insulin pump viaa control algorithm in order to automatically ensure appropriate insulininfusion. Because of its high costs, technical complexity and safetyconcerns, however, no such systems are commercially available or inroutine use.

With recent improvements in the development of CGM systems, however, LowGlucose Suspend (LGS) systems have become available. In such a system,an insulin pump is generally operated and infuses basal insulin like instandard CSII therapy according to a preset infusion schedule. A CGM,however, is additionally present and coupled to the control unit of theinsulin pump. In case of the occurrence of a hypoglycaemia—detected bythe glucose level falling below a low shutoff threshold—the pump isautomatically shut off, resulting in insulin infusion being suspended,and a warning or alarm is provided. Infusion according to the schedulemay be resumed automatically after a preset suspend time, of, e.g., 2 h,upon the glucose level rising above the threshold, or manually by thediabetic after resolving the situation. Such a system is disclosed in WO2006/083831 A1, a commercial system is known as MiniMed Paradigm VEO byMedtronic MiniMed, Inc.

In practice, however, the advantages of systems as described above islimited by drawbacks that at least significantly reduce the practicalvalue. Current LGS or similar approaches act in a static way, based onpre-programmed glucose thresholds. In order to safely prevent nocturnalhypoglycaemia, the low shutoff threshold is typically set to acomparatively high glucose level, the occurrence of which wouldgenerally not be a reason for concern as long as the diabetic is awakeand conscious. A considerable number of erroneous shutoffs or “falsealarms” is therefore known to occur. In addition, a fixed shutoffthreshold is not considered to be appropriate in all situations. Duringdaytime, an office worker may, for example, be willing to accept or evenstrive at comparatively low glucose levels in order to avoid long-termcomplications that are known to be associated with frequenthyperglycaemias. In a business meeting or when driving a car, she or hemay whish to ensure a somewhat higher glucose level to safely avoidhypoglycaemias where—at the best—concentration, the ability to respond,and the general motor behaviour are aversively affected, while amoderate hyperglycaemia causes by far less concern when occurringoccasionally and for a comparatively short time period only.

SUMMARY

The present disclosure teaches control units for pump units as used indiabetes therapy systems for CSII therapy, corresponding diabetestherapy systems and methods of operating such systems which improve thesituation with respect to the handling of hypoglycaemias and can beprovided based on proven and established technology and at reasonablecosts that are comparable to current systems.

Disclosed is, in one aspect, a control unit for an electronicallycontrolled pump unit, the control unit being designed to control thepump unit to infuse insulin into a diabetic's body in a substantiallycontinuous way according to a preset infusion schedule as a function oftime. In typical embodiments, the control unit is further designed tocontrol the pump unit to additionally infuse insulin boli on demandand—in some embodiments—an overshot bolus as will be discussed below.

The pump unit may be designed according to principles that are known inthe art. The pump unit may especially be designed as syringe driverunit, typically comprising an electric motor that is coupled to a lineardisplacement spindle. In operation, an end section of the spindle iscoupled to a displaceable piston of a syringe-like insulin container.Controlled operation of the motor results in corresponding amounts ofliquid insulin being displaced out of the container and being infused.Designs that may be used in the context of the present disclosure aredisclosed, e.g., in the WO 2010/055504 A1, WO 01/72358 A1, WO2009/077143 A1, or WO 00/25844 A1. Alternatively, the pump unit may bedesigned as disposable dosing unit as disclosed in the WO 2008/110263 A1and the WO2010/028719 A1. The pump unit may alternatively be designedaccording to further principles that are known in the art for this typeof application, for example as micro-membrane pump or micro peristalticpump.

The control unit is typically based on solid-state technology, with atleast part of the functionality being implemented as firmware code inone or more microcontrollers, ASICS, or the like. The control unit mayfurther include components such as a real-time clock, static and/ordynamic memory that stores information such as the preset infusionschedule, watch dogs, power supply and power management circuitry, andthe like. The control unit may further include or be coupled to a userinterface and a data interface for communication with devices such asCGM systems, general glucose meters, standard computers (PCs), cellphones, and the like via wired or wireless connection. Further aspectsof typical control units will be discussed below. The control unit mayespecially be part of a diabetes therapy system as will be discussedbelow in more detail, and may be realized fully or partly integral withfurther units or devices of such a system.

Typically, the control unit is—at least in part—realized with the pumpunit in an integral way in form of a generally self-contained infusionpump device, while other parts and components of the control unit may bepart of the same or a different physical device. In such an embodiment,control unit and pump unit are normally in wired or galvanic coupling.Dependent on the overall device, however, transmission of power and/orcontrol signals as well as feedback signals may be wireless.

In accordance with an aspect of the present disclosure, the control unitincludes an intervention unit. The intervention is designed tocontinuously evaluate a glucose indicative input for detecting an actualor expected hypoglycaemia and to execute, in response to an actual orexpected hypoglycaemia, a temporary hypoglycaemia intervention. Thehypoglycaemia intervention includes, for an intervention time interval,overriding the preset infusion schedule by temporarily suspendinginsulin infusion or temporarily reducing insulin infusion below thepreset infusion schedule. Here and in the following, “intervention”generally refers to a hypoglycaemia intervention where not explicitlystated differently.

The intervention unit is designed to adapt its way of operation withrespect to executing the hypoglycaemia intervention in dependence of acontrol signal. The control unit is designed to automatically generatethe control signal as a function of time and/or based on sensor input.The control signal is separate, i.e., different and independent, fromthe glucose-indicative input. The control signal is typically a signalthat is generated in dependence of time or is a sensor signal or derivedfrom a sensor signal. Adaption can be carried out during continuousinsulin infusion by the pump unit. The intervention unit may adapt itsway of operation during regular operation, i.e., during the control unitcontrolling the pump unit to infusion insulin according to the presetinfusion schedule.

The control unit automatically generating the control signal as afunction of time and/or based on sensor input implies that the controlsignal is different from a static configuration parameter setting by adevice user, e.g., for generally enabling/disabling the interventionunit and/or static setting of intervention parameters, such asintervention thresholds as will be further described below.

Continuously receiving and evaluating the glucose indicative inputimplies that these steps may be carried in a truly continuous way or ina virtually or substantially continuous way, i.e., with an interval thatis short as compared to the glucose dynamics and may, e.g., be in arange up to 15 min, e.g., 1 sec, 10 sec, 30 sec, 1 min, 2 min, 2 min, 5min, 10 min or 15 min.

Designing the intervention unit in this way allows appropriate operationin different situations and under varying conditions. As will bediscussed below in the context of exemplary embodiments, such design ofthe intervention unit avoids or at least significantly reduces thedisadvantages and drawbacks that are associated with prior art systems,such as “false alarms” that are common for the known LGS feature asdiscussed above.

Because the pump unit generally operates according to a preset scheduleand the intervention unit only comes into action—in accordance with thecontrol signal—in specific situations that require well-defined reactivemeasures, the technical complexity and risks of a closed-loop system areavoided. Furthermore, the disclosed intervention unit can, in variousembodiments, be implemented with moderate firmware effort and no orlittle additional hardware effort in a cost-efficient way.

Interaction between the control unit as a whole and the hypoglycaemiaintervention unit may generally be carried out in two alternative ways.According to the first alternative, the control unit generally controlsthe pump unit to infuse insulin according to the preset infusionschedule, and an intervention trigger signal or intervention triggercommand is generated by the intervention unit if a hypoglycaemiaintervention shall be executed. Generation of the intervention triggersignal or intervention trigger command accordingly results in overridingthe preset infusion schedule. This type of embodiment has the particularcharacteristic of the control unit ensuring normal operation accordingto the preset schedule in a case of failure, e.g., of the hypoglycaemiaintervention unit or of a CGM providing the blood-glucose indicativeinput.

According to the second alternative, the control unit generally controlsthe pump unit to override the preset infusion schedule by suspendinginsulin infusion or reducing insulin infusion below the preset infusionschedule, and an intervention suppressing signal or interventionsuppressing command is generated by the intervention unit as long as nointervention shall be initiated, i.e., during regular operation.Generation of the intervention suppressing signal or interventionsuppressing command accordingly results in the pump unit carrying outthe infusion according to a preset infusion schedule. Upon theintervention suppressing signal or intervention suppressing command notbeing present, the hypoglycaemia intervention unit is automaticallycarried out. The intervention suppressing signal or interventionsuppressing command is favourably generated continuously as long as nointervention shall be carried out. This type of embodiment has theparticular characteristic of the control unit enforcing a safe statewhere no potentially dangerous amounts of insulin may be infused in acase of failure, e.g., of the hypoglycaemia intervention unit or of aCGM providing the blood-glucose indicative input.

The intervention unit may be designed to execute the hypoglycaemiaintervention upon a glucose value of the diabetic falling below a lowerintervention threshold.

Glucose values that serve as glucose indicative input for theintervention unit may be actual measurement values or signals.Alternatively, however, it may be predicted values or signals. In thiscase, a glucose prediction unit is present that may, e.g., be part ofthe control unit or a CGM. Considerable effort has been spent indeveloping methods and algorithms for glucose prediction orextrapolation, and a variety of methods is available that may be used inthe context of the present disclosure and may be based, e.g., on linearor non-linear extrapolation. Suited algorithms are disclosed, e.g., inthe WO 2006/083831 A1. In the context of the present disclosure, glucoseprediction allows carrying out a hypoglycaemia intervention proactivelyat a point in time when the occurrence of a hypoglycaemia requiring anintervention is not yet present but can be expected to occur in the nearfuture. An alternative to a prediction algorithm which may becomputational demanding, complex and potentially susceptible to datamisinterpretation, is a comparatively aggressive fixed lowerintervention threshold as will be explained below may be used.

Completely suspending insulin infusion is a comparatively drastic oraggressive measure that can, however, be expected to be appropriate andeffective in preventing severe hypoglycaemias, in particular duringnight time. It may, however, be too drastic and result in an alsoundesired following hyperglycaemia, depending on the circumstances andspecifics of the diabetic.

Therefore, it may, in a situation of hypoglycaemia, be appropriate toonly reduce insulin infusion, while avoiding a complete suspend orshutoff. The reduced insulin infusion may generally still follow thepreset schedule, with the scheduled infusion rate being reduced, e.g.,in a proportional way, by a reduction factor <1. The reduction factormay, for example, be 0.5 (resulting in the infused amounts being halvedto 50% of the scheduled infusion rate), or 0.3 (resulting in the infusedamounts being 30% of the scheduled infusion rate). A reduction factor ofzero is accordingly equivalent to a full suspend or shut-off.Alternatively to a proportional reduction, the infusion rate may, forthe time of the intervention, be set to a low constant value. It may,e.g., be set to a rate of 0.1 IU/h to 0.3 IU/h (International Units perhour). A reduction factor and/or a constant rate to which insulininfusion may be temporarily set may be preset configuration parametersthat are typically set and tuned by a healthcare professional. Furthervariants that are based on a successive reduction of the insulininfusion will be explained further below.

The glucose indicative input may be a glucose value. A glucose value maybe provided by a spot glucose meter that is operatively coupled to thecontrol unit to transfer a measured glucose value to the control unit.Alternatively, glucose values may be manually entered via a userinterface. In a further configuration, the glucose indicative input maybe given by a glucose value that is provided by a CGM that monitors thediabetic's glucose level continuously or quasi continuously, e.g., witha measurement interval of a few minutes. While single-spot measurementsmay often be sufficient during daytime, continuous glucose monitoring isparticular advantageous if it is desired to automatically detect asituation of actual or expected hypoglycaemia, in particular duringnocturnal sleeping time, during an extended business meeting, whendriving a car, or the like.

Along with or as part of the hypoglycaemia intervention, a notificationor alert may be provided via an alerting unit. The alerting unit may,e.g., be or include an optical indicator such as an (O)LED or a display,an acoustic indicator such as a buzzer or loud speaker, or a tactileindicator, such as a pager vibrator. Such indicators are typicallypresent in diabetes therapy systems and devices for alerting andalarming as well as for general user feedback purposes. Alerting may beselectively activated or deactivated and/or the type of alert may beselected by an alert control signal. An acoustic and a tactileindication may be provided during night time in order to waken thediabetic and make him or her aware of a metabolic situation that mayneed immediately be taken care of, such as a hypoglycaemia, while thismay not be necessary and desired at daytime for a diabetic with normalhypoglycaemia awareness.

The intervention unit may be designed to terminate the hypoglycaemiaintervention a given time interval after staring the hypoglycaemiaintervention, or upon a glucose value of the diabetic rising above anupper intervention threshold, or upon a resuming command provided by auser.

In case of terminating the intervention a given time interval afterstarting the hypoglycaemia intervention, this time interval can be theintervention time interval.

After termination of the hypoglycaemia intervention, infusion accordingto the preset schedule may be directly resumed. Alternatively, specialsteps may be carried out to prevent subsequent complications resultingfrom the suspended or reduced infusion during the intervention timeinterval. Those steps may especially include the administration of anovershot bolus as will be explained further below.

A glucose value that serves as basis for terminating the hypoglycaemiaintervention may be provided as glucose indicative input in the sameways as discussed above. In case a glucose value is provided as spotmonitoring value, the control unit favourably includes a reminder timerthat is started along with the hypoglycaemia intervention and remindsthe diabetic to do a further measurement after a alerting interval of,e.g., 30 min, 45 min, or 60 min has lapsed. In dependence of the glucosevalue, the intervention unit may either terminate the hypoglycaemiaintervention, resulting in infusion being resumed according to thepreset schedule, or continue with the intervention in case the glucosevalue is still low. In this case, the reminder timer is favourablyre-triggered with the same or a different alerting interval.

In a variant, insulin infusion according to the preset schedule isresumed upon a glucose value of the diabetic rising above an upperintervention threshold, but not before expiry of a preset minimumintervention time interval.

In case of both a lower and an upper intervention threshold beingpresent, the upper intervention threshold may be identical to the lowerthreshold. Alternatively, the upper intervention threshold may beselected above the lower intervention threshold for safety reasons andto provide some hysteresis which is favourable with respect tooperational stability.

The control signal may include at least one of the lower interventionthreshold and the upper intervention threshold. Alternatively oradditionally, the control signal may include a reduced level of insulininfusion below the preset schedule and/or the intervention timeinterval. As described before, a reduced level of insulin infusion mayin particular be defined as reduction factor as compared to the presetschedule or as a fixed infusion rate.

All of these control signals have the result of the intervention unitoperating, in dependence of the control signal, in a more conservativeor more aggressive way.

In the present context, “conservative” generally means that ahypoglycaemia intervention is carried out at (comparatively) low glucoselevels only, and/or that the physiological effect of a hypoglycaemiaintervention is comparatively small or limited. The intervention unitmay accordingly come into action and overrule the preset schedule onlyif a hypoglycaemia is almost certainly given or to be expected.Additionally or alternatively, the effect of the intervention may becomparatively small as compared to infusion without hypoglycaemiainterventions. While “false alarms” can be safely avoided in this case,an actual moderate hypoglycaemia may not be detected in some cases.

“Aggressive” generally means that a hypoglycaemia intervention iscarried out already at (comparatively) high glucose levels, and/or thatthe physiological effect of a hypoglycaemia intervention iscomparatively large. In this case, the occurrence of actualhypoglycaemic excursions can be prevented with high certainty, while“false alarms” may be somewhat more likely to occur as compared to the“conservative case”, potentially resulting in undesired hyperglycaemias.

Via the control signal, different levels of “aggressiveness” may beselected. The intervention unit may, for example, be controlled to actin a comparatively conservative way during daytime in order to prevent“false alarms”, but to act more aggressively during nocturnal sleep orsimilar situations in order to safely prevent the occurrence ofhypoglycaemic excursion in this critical phase as will be explainedfurther below.

The intervention unit may be designed to adapt its way of operationduring execution of the hypo-glycaemia intervention. Adapting the way ofoperation of the hypoglycaemia intervention unit may especially becarried out in dependence of the diabetic's glucose course as explainedin the following.

The intervention unit may be designed, when executing the hypoglycaemiaintervention, to successively reduce insulin infusion and/or, whenterminating the hypoglycaemia intervention, to successively increaseinsulin infusion back to the preset schedule. Such successive reductionof insulin infusion when executing the hypoglycaemia intervention may,e.g., be carried out in a number of discrete reduction levels (RLs), forexample

RL1 reduction to 80% of preset schedule

RL2 reduction to 60% of preset schedule

RL3 reduction to 40% of preset schedule

RL4 reduction to 20% of preset schedule

RL5 reduction to 0 (corresponding to a full suspend)

Operation of such an intervention unit is further explained withreference to FIG. 5, schematically illustrating exemplary ways ofoperation of a control unit and an intervention unit with a number ofdiscrete reduction levels. Curves 200, 210, illustrate a more moderateand an alternative more aggressive way of operation of the hypoglycaemiaintervention unit. Curves 200, 210 show, on the vertical axis, theinsulin infusion while a hypoglycaemia intervention is carried out aspercentage of the infusion according to preset schedule as a function oftime on the horizontal axis. The hypoglycaemia intervention begins attime t₀and is terminated at time t₁.

Change between the individual reduction levels may be carried out independence of the diabetic's glucose course during the hypoglycaemiaintervention. The intervention may, e.g., start with moderate level RL1.If the glucose values do not rise in the following or continues falling,a further reduction to RL2 may be carried out, and so forth. Forconservative curve 200, reduction ends at a minimum reduction level RL3.Alternatively, stepwise reduction may be continued, to any other minimumreduction level, potentially up to a potential full suspend. A number ofglucose thresholds GT1 . . . GT5 (not shown in FIG. 5), corresponding tothe above-given exemplary reduction levels RL1 . . . RL5, may be definedand stored by the control unit or the intervention unit, with GT1 as thehighest glucose value corresponding to the lower intervention thresholdat which the hypoglycaemia intervention is carried out. While thesuccession between the reduction levels is shown with equal timeintervals, they will, for this type of embodiment, typically not beequal but depend on the diabetic's glucose course during thehypoglycaemia intervention. Additionally, a switch to reduction levelsRL2 and/or reduction level RL3 may not occur if the diabetic's glucosevalue starts rising sufficiently fast.

The more aggressive way of operation of the hypoglycaemia interventionunit, illustrated by curve 210, differs from the more moderate behaviourmainly by a steeper decrease of the infusion and a lower minimuminfusion level, in curve 210 shown as full suspend of infusion toreduction level RL5.

A successive increase of the infusion, thus returning to the presetschedule, may be carried out additionally or alternatively in ananalogue way, as illustrated the rising edges of curves 200, 210. In avariant, insulin infusion is reduced to a minimum level or fullysuspended right at the beginning of the hypoglycaemia intervention,while resuming infusion according to the preset schedule is carried outsuccessively, using, e.g., the above-given levels. For such anembodiment, the falling left edge of curves 200, 210 would be vertical.Likewise, it is possible to reduce the infusion successively and toresume infusion according to the preset schedule directly withoutintermediate steps. For such an embodiment, the rising right edge ofcurves 200, 210 would be vertical.

Alternatively to a successive reduction and/or resuming of insulininfusion in dependence of the diabetic's glucose course, the controlunit may be designed to store a preset successive reduction regimeand/or a preset successive resuming regime and to execute ahypoglycaemia intervention according to the preset regime. Such a regimemay, e.g., include a stepwise reduction of the infusion with theabove-given reduction levels according to the left falling edges ofcurves 200, 210. The time interval between the single reduction stepsmay, e.g., 15 min each. Once the beginning of a hypoglycaemiaintervention has started, successive reduction to the minimum level orfull suspense is then carried out according to the preset reductionregime, independent of the course of the diabetic's glucose value.Resuming may be carried out in a single step or according to a presetsuccessive resuming regime. For an embodiment where the duration of theintervention time interval is given, a hypoglycaemia intervention may,from beginning to end, accordingly be defined by a reduction-vs-timecurve, like curves 200, 210.

The intervention unit may be designed to determine a level of reductionof insulin infusion below the preset schedule and/or the interventiontime interval in dependence of the blood-glucose indicative input. Theblood indicative input may, e.g., be a glucose level or a glucose trendat the beginning of the hypoglycaemia intervention. This type ofembodiment allows to automatically adapt the aggressiveness level of thehypoglycaemia intervention in dependence of the glucose.

In an example, a reduction to above-defined level RL1 is carried out fora glucose value below glucose threshold GT1 as explained above or aglucose trend indication that the glucose value will slowly fall belowthis threshold. For a rapid glucose decrease, indicating, e.g., that theglucose value has, starting from a value above GT1, rapidly fallen orwill rapidly fall below GT4 or GT5, the hypoglycaemia intervention mayaccordingly be carried out with a reduction to RL4 or RL5.

The control unit may include a clock unit and may be configured togenerate the control signal in dependence of a time of day.

The control signal may include an enablement signal and the interventionunit may be designed to selectively enable or disable execution of thehypoglycaemia intervention in dependence of the enablement signal.Disabling the hypoglycaemia intervention is a limit case of“conservative” behaviour and results in the control unit and the pumpunit to temporarily operate in the same way as if no intervention unitwas present. Alternatively to providing a dedicated enablement signal,it is, in some embodiments, generally possible to temporarily disable ordeactivate the intervention unit by setting a lower interventionthreshold that is higher than a glucose value that may be expected tooccur in practice.

In embodiments where the intervention unit is designed to execute,besides the hypoglycaemia intervention, one or more furtherintervention, such as a hyperglycaemia intervention, or in case morethan one intervention unit is present in parallel, the same enablementsignal may be used for enabling and disabling the execution of thehypoglycaemia intervention and further interventions. Alternatively,separate enablement signals may be foreseen.

In embodiments involving a time-of-day dependent enablement signal,executing the hypoglycaemia intervention may be automatically enabledduring nighttimes and may be disabled, i.e., deactivated, during daytimewhere the diabetic would normally become aware of a situation requiringan intervention and the optional accompanying alerts would bedisturbing, e.g., during a business meeting or in a public environment.

Time-of-day dependent control parameters that are provided as controlsignal to the intervention unit may be preset and stored as controlparameter profile in typically non-volatile memory, similar to the basalinfusion schedule. Different control signal profiles may further bepresent for different days of the week, e.g., for working days andweekends. With respect to weekends, it may, e.g., be considered that thediabetic may have the habit to take a nap after lunch that should bedealt with in the same ways a nocturnal sleep.

The control unit may include or may be designed to operatively couple toa physical activity sensor—in particular one or more of anaccelerometer, a pedometer, a pulse meter, an oxymeter, a breath sensor,body temperature sensors, hart rate sensors, ventilation rate sensors,amount of sweat and blood oxygen saturation sensors, EEG sensors and ECGsensors—and may be designed to generate the control signal in dependenceof physical activity of the diabetic.

The control unit may be especially be designed to enable the executionof the hypoglycaemia intervention at high physical activity, inparticular upon the physical activity sensor indicating sportiveactivity or exercise of the diabetic.

Periods of increased physical activity, such as sports or exercise, areparticularly critical with respect to the occurrence of hypoglycaemiasbecause of the increased energy consumption of the body, which causes,for diabetics, an increased hypoglycaemic risk. At the same time, thehypoglycaemia awareness is often decreased. Controlling the interventionunit in dependence of physical activity allows preventinghypoglycaemias, e.g., by setting an appropriate lower interventionthreshold, without temporarily decreasing the basal administration orsuspending insulin administration manually as precautious measure, whichis typically done according to the state of the art in an ad-hoc andoften inappropriate way. However, a temporary reduction of the infusionmay be carried out in addition. State-of-the art insulin infusiondevices typically allow such a reduction on request via user input.

Physical activity sensors may be an integral and dedicated part of thecontrol unit or an overall diabetes therapy system. They may, however,fully or partly, also be realized by commercial standard devices such asstandard pulse meters and standard pedometers that are carried by manypeople during everyday life to monitor their health state and energyconsumption, or are especially carried for training or exercise and mayalso be part of everyday electronic devices such as smart phones. Thosedevices may include an RF communication interface, such as aBluetooth/Bluetooth Low energy interface, that may favourably be usedfor operatively coupling to the control unit. Those devices often have awrist-watch like design, may be carried in a pocket, worn as necklace ormay—e.g., in case of pedometers—be included in functional clothing,sneakers, or the like.

The control unit may include or be designed to operatively couple to afasting period sensor, the fasting period sensor being designed todetermine a fasting period measure, indicating a started or anticipatedfasting period. The control unit may further be designed to generate thecontrol signal in dependence of the fasting period measure.

In the present context, the phrase “fasting period” refers to a periodwhere the diabetic does not consume significant amounts oftherapy-relevant food, in particular carbohydrates, for a prolonged timeinterval of typically a number of hours. In particular, the nocturnalsleep is considered as fasting period. The fasting period sensor may,however, also be used to indicate shorter periods such as a nap and thesame procedures may be followed.

As discussed above, nocturnal hypoglycaemias are a source of particularconcern for many diabetics and/or partners, parents, etc. and cause, insome cases, severe psychological stress. In case an execution of thehypoglycaemia intervention is normally disabled during daytime, thecontrol signal may enable the execution for the nocturnal sleepingperiod. In case executing the hypoglycaemia intervention are generallyenabled, the control signal may set different intervention thresholdsfor the night, in particular a somewhat higher value for the lowerintervention threshold as compared to daytime, in order to safelyprevent nocturnal hypoglycaemic excursions.

The control unit may be designed to enable execution of thehypoglycaemia intervention upon the fasting period measure indicatingthat the diabetic has fallen asleep, has gone to bed, or can be expectedto fall asleep or go to bed soon.

A fasting period sensor does not necessarily provide a measure that isnecessarily connected with the diabetic falling or having fallen asleepin a causal nexus. It may also be a measure that is indicative for andcorrelated with the diabetic's intention to go to bed soon, such as thepresence in the bedroom, laying in the bed, etc.

A fasting period sensor may include one or more of a geolocation sensor,an accelerometer, a pulse meter, a single or a plurality of positiontransducers carried by or attached to the diabetic, and a single or aplurality of contact sensors integrated in the diabetic's bed ormattress. The fasting period sensor may at the same time be a physicalactivity sensor as discussed above and may be realized in the same way.

A geolocation sensor, e.g., in form of a GPS sensor, may be present toverify that the diabetic is at a place where it can be assumed that heor she will go to bed soon. Position sensors that are carried at thediabetic's body may be used to determine if the diabetic is in asubstantially horizontal, i.e., lying position. Contact sensors indiabetic's bed or mattress provide an indication whether the diabeticactually is in bed.

The EP 1762259 A1 discloses further sensors that may serve as fastingperiod sensor in the present context, such as ambient light sensors. TheEP 1762259 A1 further discloses the use of a manually operated“going-to-bed” button that is operated by a diabetic substantially atthe time of going to bed. Also such a button may serve as fasting periodsensor in the present context. Further sensors may be used that arementioned above in the context of exercise or sportive activity.

While a single fasting period sensor may be sufficient under somecircumstances, it may be favourable to rely on a fusion of more then onefasting period sensor. For example, a combination of a geolocationsensor and contact sensors in the mattress may be used.

The control unit may further be designed to evaluate a time of daysignal that is provided by a clock unit and may be configured togenerate the control signal as a combination of a time of day signal incombination with signals that are provided by one or more fasting periodsensors. The control unit may especially be designed to evaluate signalsas provided by fasting period sensors only if a further condition withrespect to the time of day is met.

The control unit may, for example, be designed to enable an execution ofthe hypoglycaemia intervention if a preset going-to-bed time has beenpassed and the one or more fasting period sensor(s), e.g., a geolocationsensor, indicate that the diabetic actually is gone to bed, has gone tobed, is asleep, or will do so soon. If the time of day criterion is notmet, the intervention unit may be disabled or active with moreconservative setting as discussed above.

While requiring some additional hardware and firmware effort as comparedto a pure clock-controlled generation of the control signal as describedabove in the context of a further embodiment, control of theintervention unit is more accurate for those embodiments that include afasting period sensor.

The control unit may include or may be designed to operatively couple toa continuous glucose monitor (CGM), the CGM providing the blood-glucoseindicative input.

The control unit may be designed to determine an overshot bolus and acompensation rate based on an amount of insulin that would be infused inaccordance with the preset schedule within a compensation time intervalfollowing the hypoglycaemia intervention. The control unit may furtherbe designed, following the intervention, to control the pump unit toinfuse the overshot bolus and to control, following the infusion of theovershot bolus, the pump unit to infuse insulin temporary at thecompensation rate for the compensation time period. In some of thoseembodiments, the control unit is designed to determine the overshotbolus and the compensation rate such that the total of the overshotbolus and the amount of insulin that is administered in the compensationtime interval at the compensation rate sum up to the amount to theamount of insulin that would be administered within the compensationtime interval in accordance with the preset schedule. In other words,the amount of insulin that is actually infused in the compensation timeinterval and the overshot bolus add up to the infusion amount in thecompensation time period according to the preset schedule.Alternatively, however, the total may be larger or smaller. Thecompensation rate may be a fixed or flat rate or may generally followthe course of the preset schedule with some reduction.

While it is appropriate—in response to a detected actual or predictedhypoglycaemia, to temporarily suspend or reduce insulin infusion, it isknown in case of a suspension or reduction for a prolonged time period,exceeding, e.g., 30 min o 1 h, a lack of insulin may occur at the end ofthe intervention, resulting in a following undesired hyperglycaemia.Providing, following the intervention, an overshot bolus according tothis type of embodiment compensates for this lack of insulin. Reducingthe scheduled infusion for a limited compensation time period preventsthe overshot bolus from resulting in a further following hypoglycaemia.The control unit may be designed such that the steps of infusing anovershot bolus and following infusion at a compensation rate are carriedout if the duration of the hypoglycaemia intervention exceeds a timeperiod of, e.g., 30 min or 1 h, defined, e.g., as preset configurationparameter. The compensation time period may also be a preset parameterand be in the range, of, e.g., 1 h or 2 h.

The intervention unit may be designed to execute, in case of an actualor expected hypoglycaemia of the diabetic, a number of alternativehypoglycaemia handling routines, wherein at least one of the number ofalternative hypoglycaemia handling routines includes executinghypoglycaemia intervention. This type of embodiment increases theflexibility for reacting on an actual or expected hypoglycaemia in a waythat is both appropriate and acceptable for the diabetic in differentsituations. An alternative to the hypoglycaemia intervention asdiscussed so far may, e.g., be to propose the diabetic to consume anappropriate, typically calculated, amount of fast-acting carbohydrates,either without or with less temporary reduction of the infusion. Upondetection of an actual or expected hypoglycaemia, the diabetic may beprovided with these alternative options and select whatever isappropriate in the specific situation. In some embodiments, the controlunit may be designed to select a hypoglycaemia handling routine based,fully or partly, on the control signal. For example, the diabetic may beprovided with the options for either executing the hypoglycaemiaintervention or consuming carbohydrates during daytime while thehypoglycaemia intervention may in any case be executed in the nocturnalfasting period. In further embodiments, a hypoglycaemia handlingstrategy may be selected in dependence of the severity of an actual orexpected hypoglycaemia. For example, the hypoglycaemia intervention maybe executed in case of a moderate hypoglycaemia and the hypoglycaemiaintervention may be executed together with a proposal for consumingfast-acting carbohydrates, such as glucose, in a more severe case.

The intervention unit may be designed to execute, in response to anactual or predicted hyperglycaemia of the diabetic, a hyperglycaemiaintervention, the hyperglycaemia intervention including controlling thepump unit to infuse a correction bolus.

Under most circumstances, administration of a correction bolus is anappropriate measure in case of a hyperglycaemia, the correction bolusbeing computed to lower the glucose level to a target level or targetrange. A number of algorithms are known in the art which may differ withrespect to some computational details and with respect to consideredadditional influence factors, but are generally based on the amount bywhich the glucose value should be lowered and the diabetic's individualinsulin sensitivity, i.e., the effect of a given insulin dose on theglucose level. Under certain circumstances, however, a temporaryreduction or suspension of the insulin infusion and/or a consumption ofadditional carbohydrates may be appropriate rather than the infusion ofa correction bolus, despite a currently raised glucose value. Thisaspects will be discussed in more detail below in the context ofexemplary embodiments.

Disclosed is, in a further aspect, a diabetes therapy system, includingan pump unit, the pump unit being designed to be carried by a diabeticattached to his or her body or in proximity to his or her bodysubstantially continuously and concealed from view, and a control unitas generally disclosed above and further below in the context ofexemplary embodiments. The control unit of the diabetes therapy systemis or is designed to operatively couple to the pump unit to controloperation of the pump unit. The control unit may be realized in form ofa compact single device, optionally together with further functionalunits such as a CGM. Alternatively, the diabetes therapy system may bemade of a number of distinct an physically separate units with operativecoupling.

The diabetes therapy system may include a continuous glucose monitor(CGM). As discussed above, the CGM may operatively couple to theintervention unit to provide the control signal to the interventionunit.

According to a still further aspect, the present disclosure is directedtowards a method for controlling a pump unit to infuse insulin into adiabetic's body in a substantially continuous way according to a presetinfusion schedule as a function of time.

The method includes executing a hypoglycaemia interventions undercontrol of an intervention unit. The intervention may include detectingor an actual or expected hypoglycaemia of the diabetic and carrying out,in response to the actual or expected hypoglycaemia, a hypoglycaemiaintervention. The hypoglycaemia intervention includes overriding, inresponse to the detected or predicted hypoglycaemia, the preset infusionschedule by temporarily suspending insulin infusion or by temporarilyreducing insulin infusion below the preset schedule. The method furtherincludes automatically generating a control signal as a function of timeand/or based on sensor input and adapting the way of operation of theintervention unit with respect to the hypoglycaemia intervention independence of the control signal.

The method for controlling a pump unit may especially be carried out bya control unit including an intervention unit as generally discussedabove as well as further below in the context of exemplary embodiments.In this description, some aspects of the present disclosure are givenwith main reference to the method while others are given mainly withreference to structural units or hardware units, such as control unitsand diabetes therapy systems as best suited for a clear and concisepresentation. It shall be understood, however, that embodiments ofhardware units at the same time define corresponding method embodimentsand vice versa.

According to a still further aspect, the present disclosure is directedto a computer program product storing executable code as well as towardsa tangible computer-readable medium storing the code. The code, whenexecuted, implements functionally of a controller unit including anintervention unit and/or executes a method as generally discussed aboveand further below in the context of exemplary embodiments.

The above-given disclosure as well as the discussion of exemplaryembodiments further below includes a number of aspects for control unitsincluding an intervention unit that do not necessarily rely on thepresence of a control signal as discussed above.

In this respect, disclosed is a control unit for an electronicallycontrolled pump unit, the control unit being designed to control thepump unit to infuse insulin into a diabetic's body in a substantiallycontinuous way according to a preset infusion schedule as a function oftime, the control unit including an intervention unit, the interventionunit being designed to continuously evaluate a blood-glucose indicativeinput for detecting an actual or expected hypoglycaemia and to execute,in response to an actual or expected hypoglycaemia, a temporaryhypoglycaemia intervention, the hypoglycaemia intervention including,for an intervention time interval, overriding the preset infusionschedule by temporarily suspending insulin infusion or temporarilyreducing insulin infusion below the preset infusion schedule.

The intervention unit is designed

-   -   to adapt its way of operation during execution of the        hypoglycaemia intervention, and/or    -   when executing the hypoglycaemia intervention, to successively        reduce insulin infusion and/or, when terminating the        hypoglycaemia intervention, to successively resume insulin        infusion back to the preset schedule, and/or        to determine a level of reduction of insulin infusion below the        preset schedule and/or the intervention time interval in        dependence of the blood-glucose indicative input.

Additionally or alternatively, the control unit may be designed togenerally control the pump unit to override the preset infusion scheduleby suspending insulin infusion or reducing insulin infusion below thepreset infusion schedule, and the intervention unit may designed togenerate an intervention suppressing signal or intervention suppressingcommand as long as no intervention shall be initiated. The disclosure ofany of such control units implicitly also discloses a correspondingmethod for controlling a pump unit, the method being carried out byoperating the control unit.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-mentioned aspects of exemplary embodiments will become moreapparent and will be better understood by reference to the followingdescription of the embodiments taken in conjunction with theaccompanying drawings, wherein:

FIG. 1 shows an exemplary embodiment of a diabetes therapy system in aschematic structural view.

FIGS. 2a, 2b show exemplary control signals.

FIG. 3 shows an exemplary operational flow for a hypoglycaemiaintervention in a system according to FIG. 1.

FIG. 4 shows a further exemplary embodiment of a diabetes therapy devicein a schematic structural view.

FIG. 5 illustrates exemplary ways of operation of control units inaccordance with the present disclosure (discussed before).

DESCRIPTION

The embodiments described below are not intended to be exhaustive or tolimit the invention to the precise forms disclosed in the followingdescription. Rather, the embodiments are chosen and described so thatothers skilled in the art may appreciate and understand the principlesand practices of this disclosure.

The exemplary diabetes therapy system of FIG. 1 includes, in anoperational state, a compact and self-contained infusion pump device 1.Infusion pump device 1 includes a pump unit 11 and a control unit 12.Pump unit 11 is in the following exemplarily considered as being asyringe driver pump with a motor-driven threaded spindle. Pump unit 11may, however, alternatively be designed according to another principleas discussed above.

Control unit 12 is realized by microcontroller-based solid statecircuitry as generally known in the art. Control unit 12 includes pumpdriver 121, memory 122, clock unit 123, and intervention unit 124.Memory 122 is non-volatile and stores a circadian infusion schedule.During normal operation where no intervention is carried out, atime-of-day signal that is provided by clock unit 123 and the infusionschedule as stored in memory 122 are fed into pump driver 121 and pumpdriver 121 drives and operates pump unit 11 in accordance with theinfusion schedule and the time of day.

The time of day signal is further fed from clock unit 123 intointervention unit 124 as control signal, resulting in operation ofintervention unit 124 to adapt and vary its behaviour in accordance withthe time of day, as will be discussed below in more detail.

The exemplary diabetes therapy system of FIG. 1 further includes acontinuous glucose monitor (CGM) 2 that is carried by the diabetic anddetermines its glucose level in a continuous or quasi continuous way.CGM 2 is operatively coupled to intervention unit 124 for transmittingand feeding an output signal into intervention unit 124 as glucoseindicative input. While a number of technologies are available forestablishing the operative coupling, such as a wired connection, aninfra red (IR) connection, a wireless short range radio frequency (RF)link is assumed in the following, the RF link being realized, e.g.,according to the Bluetooth standard. CGM 2 may directly transmit thecontinuous measured glucose date. Alternatively, however, some degree ofprocessing may be carried out in CGM 2, such as noise reduction, peakdetection, trend analysis, etc.

Like in the following discussion of further exemplary embodiments, FIG.1 only shows those structural and functional features as well as theirinteraction that are of particular relevance in the context of thepresent disclosure, without excluding the presence of further features,components and interactions. Infusion pump device 1 may, e.g., include apower supply, such as rechargeable and/or non-rechargeable batteries, auser interface, wired and/or wireless communication interfaces, powermanagement circuitry, watchdog and further safety circuitry, and thelike.

As discussed above in context of the general disclosure, a (not shown)alerting unit may be present and operatively coupled to interventionunit 124 to provide a user alert in case of an intervention. Theexemplary system of FIG. 1 further includes an optional remote controlunit 3 that is operatively coupled to control unit 12 of infusion pumpdevice 1, favourably via a wireless communication interface, based,e.g., on the Bluetooth standard or the like. Remote control unit 3includes a user interface with, e.g., some or all of a display, an audioaltering unit, a tactile alerting unit, push buttons, switches, a touchscreen, and the like. Remote control unit 3 may be used by the diabeticfor controlling operation of the diabetes therapy system in daily use.Remote control unit 3 may further include advanced functions fordetermining insulin boli to be infused in the context of food intakeand/or for lowering raised glucose values, and may further includefunctionality such as therapy statistics. Remote control unit 3 mayfurther serve as relay to couple infusion pump device 1 and/or CGM 2 toa remote computer, e.g., for configuration and/or data archivingpurposes. Embodiments of remote control unit 3 may further include aglucose meter. A remote control unit 3 may, in summary, offerfunctionality as known, e.g., from ACCU-CHEK® Aviva Combo devices asprovided by Roche Diagnostics, or as disclosed in the EP 01920640 A1.

As further indicated in FIG. 1, remote control unit 3 may operativelycouple to CGM 2. In such an embodiment, remote control unit 3 may bedesigned to receive and evaluate glucose data from CGM 2 substantiallycontinuously, in given time intervals of, e.g., some minutes up to 1 hand/or on request. Remote control unit 3 may store those data for diarykeeping purposes and may display those data as well as trends and/orwarnings that are derived from those data, e.g., in form of a glucoseversus time curve on a display of remote control unit 3. A spot glucosemeter provided in remote control unit 3 may further generate calibrationdata for CGM 2.

In embodiments where remote control unit 3 is present, it is generallypossible to operatively couple CGM 2 to control unit 12 via remotecontrol unit 3 as relay. In this case, however, executing anintervention as discussed below requires remote control unit 3 to begenerally present and operating. Therefore, a direct and independentoperatively coupling may be provided between CGM 2 and control unit 12to provide the glucose indicative input to interaction unit 124, whetheror not an operatively coupling between CGM 2 and remote control unit 3is provided, as indicated in FIG. 1.

In FIG. 1, like in FIG. 4 discussed further below, solid lines betweenfunctional units indicate a typically galvanic or wired coupling, withthe corresponding connected components being typically realized in acommon physical unit. Dashed lines indicate wireless operativelycoupling between typically separate and remote physical units. Inalternative embodiments, however, the design as wired or wirelesscoupling may be different, in dependence of the overall architecture.They are therefore not to be understood as limiting.

It is further to be understood that the shown differentiation betweenindividual functional units is mainly made to clarify the operationalrelation and interaction between functional units. In practice, some ofthose units may be realized by a single physical component, such as amicrocontroller, or distributed between a number of physical components.For example, memory 122 and clock unit 123 may be realized together withintervention unit 124 in a single microcontroller generally representingcontrol unit 12. Typically, all or some of the functionality isimplemented as firmware code in a single or a number ofmicrocontrollers, ASICS, and the like.

FIG. 2a illustrates an exemplary control signal for intervention unit124. In this embodiment, the control signal is given by a binary signalA as enablement signal. Logic “1” indicates that execution of thehypoglycaemia intervention is enabled while logic “0” indicates thatexecution of the intervention is disabled. In FIG. 2a , signal “A” isshown as function of time t for a circadian cycle from midnight tomidnight. Execution of the hypoglycaemia intervention is enabled fromabout 23:00 to 6:00 and disabled otherwise. The time where execution isenabled corresponds to the diabetic's typical fasting periods duringnocturnal sleep while the time where execution is corresponds to thediabetic's daytime. The times of day where interventions are enabled anddisabled, respectively, are favourably therapy parameters that arestored in non-volatile memory of control unit 12, for example in memory122.

As discussed above in the context of the general description, thehypoglycaemia intervention may either cause a complete temporary suspendof insulin infusion by pump unit 11 or a temporary infusion at reducedrate below the preset infusion schedule as stored in memory 122. For theembodiment of FIG. 2a , the intervention is executed upon the diabetic'sglucose value falling a lower intervention threshold of, e.g., 70 mg/dl,the low intervention threshold being a pre-set parameter that is storedin non-volatile memory of control unit 12. As discussed above in thecontext of the general description, the intervention may be terminatedand infusion according to the preset schedule may be resumed a givenintervention time interval after beginning of the intervention, or uponthe glucose value rising above an upper intervention threshold, with theintervention time interval or the upper intervention threshold beingstored parameters.

FIG. 2b schematically illustrates the course of a circadian controlsignal for an alternative embodiment of intervention unit 124. For thisembodiment, executing the hypoglycaemia intervention is enabled at alltimes of the day. The control signal, however, varies the lowerintervention threshold in dependence of the time of day, as reflected bythe course of signal “L”. From about 23:00 to 6:00, the lowerintervention threshold is set to 70 mg/dl, and is set to 50 mg/dl forthe rest of the day where the diabetic is awake. From 6:00 to 23:00, thehypoglycaemia intervention is accordingly carried out upon the glucosevalue falling below 50 mg/dl, while it is carried out upon the glucosevalue falling below 70 mg/dl from 23:00 to 6:00, resulting in a moreaggressive nocturnal operation of intervention unit 124 as compared to amore conservative operation for the rest of the day.

In addition to the lower intervention threshold, FIG. 2b shows a timevarying upper intervention threshold for terminating the hypoglycaemiaintervention as further component of the control signal, reflected bythe course of signal “U”. In the example, the upper interventionthreshold is set to 120 mg/dl for the nocturnal time from 23:00 to 6:00and to 90 mg/dl for the rest of the day. Alternatively to atime-dependent upper intervention threshold, a time variable lowerintervention threshold may be used in combination with a presetintervention time period.

Alternatively to clock unit 123 providing a signal of the form as shownin FIG. 2a, 2b to intervention unit 124, clock unit 123 may provide thetime of day signal as such to intervention unit 124, with a signal asshown in FIG. 2a, 2b being generated internally by intervention unit124.

FIG. 3 illustrates the major steps of an operational flow for anembodiment in accordance with FIG. 1, with an enablement signal as shownin FIG. 2a . In this example, preset lower and upper interventionthresholds are assumed. Like in further examples that will be discussedbelow, control of the single steps is carried out under control ofcontrol unit 12.

In step S1, pump unit 11 is controlled in accordance with the scheduleas stored in memory 122 and no hypoglycaemia intervention is executed.Unless an intervention is carried out and infusion according to thepreset schedule is overruled, infusion according to the preset scheduleis assumed to continue during the following steps. In step S2, a glucosevalue is received from CGM 2 as glucose indicative input. In step S3,the received glucose value is evaluated by determining whether the valuereceived in step S2 is below the lower intervention threshold. If thisis not the case, infusion according to the preset schedule in step S1 iscontinued.

If the glucose value is below the lower intervention threshold, theenablement signal is evaluated step S4. That is, it is determinedwhether or not execution of the hypoglycaemia intervention is enabled.If execution is disabled, infusion according to the preset schedule instep S1 is continued.

If execution of the hypoglycaemia intervention is enabled, interventionunit 124 starts overriding the administration schedule in step S5. Inthis description, it is assumed that hypoglycaemia intervention unit 124is designed to either temporarily suspend insulin infusion or to reduceinfusion in a single step. In variants, however, intervention unit 124may be designed to successively reduce the insulin infusion according toa preset regime or in dependence of the glucose course, as discussedabove in the general description in context of FIG. 5. Likewise, whensubsequently resuming infusion (step S6 as discussed below), resuming isexemplarily assumed to be done in a single step. Alternatively, resuminginfusion may be carried out successively. Successive reduction orresuming of the insulin delivery may, e.g., be carried out in a numberof discrete steps or in a continuous way.

In step S6, a next glucose value is received from CGM 2. In step S7, theglucose value is evaluated by determining whether the glucose valuereceived in step S6 is below the upper intervention threshold. If thisis not the case, i.e., if the glucose value has, between step S2 andstep S6, raised above the upper intervention threshold, thehypoglycaemia intervention is terminated and infusion according to thepreset schedule in step S1 is resumed. Otherwise, the intervention iscontinued and a next glucose value is received in step S6.

While FIG. 3 illustrates a basic exemplary operational flow, a number ofmodifications and alternative ways and orders of carrying out the singlesteps are well possible. In the embodiment of FIG. 3, for example, anintervention, once started in step S5, is continued until it isdetermined in step S7 that the glucose value has risen above the upperintervention threshold, independent of the further course of theenablement signal. By evaluating the enablement signal during theintervention it is alternatively possible to terminate the interventionupon the execution of interventions being disabled via the enablementsignal.

As described above, a user alert may further be provided by activatingan alerting unit along with starting the hypoglycaemia intervention instep S5.

In further variants, a user input is requested as confirmation beforestarting an intervention in step S5 and/or terminating it in step S7. Infurther variants, after beginning the hypoglycaemia intervention in stepS5, a delay may be provided to ensure that the intervention, oncestarted, is executed at least for a minimum intervention time period.Similarly, the hypoglycaemia intervention may only be started if theglucose value stays below the lower intervention threshold for a presetminimum time period and/or may be terminated only if it continuouslystays above the upper intervention threshold for a preset minimum timeperiod.

Intervention unit 124 may, fully or partly, be realized integral with acontrol unit of CGM 2. In particular, comparing a measured or predictedglucose value with a lower and/or upper intervention threshold may becarried out in CGM 2 and a trigger signal may be transmitted from CGM 2to infusion pump device 1 only if the lower or upper interventionthresholds are fallen below or raised beyond, respectively.

In the example of FIG. 3, glucose values are received and evaluatedsubstantially continuously in steps S3, S6, independent form theenablement signal. This is generally considered favourable sincediabetics carrying a CGM typically want to continuously track theirglucose level. By exchanging step S2 and Step S3, however, it is alsopossible to receive and evaluate data from CGM 2 only if execution ofthe hypoglycaemia intervention is enabled.

FIG. 4 shows a further exemplary embodiment of a diabetes therapy systemin a schematic functional view. The general design and operation issimilar to the embodiment as shown in FIG. 1, with the followingdiscussion being focussed on differentiating aspects. While the controlsignal for intervention unit 124 in FIG. 1 is given by a time of daysignal that is provided by clock unit 123, intervention unit 124 a ofFIG. 4 receives and evaluates additional input from sensors 4 a, 4 b.

For the moment, sensors 4 a, 4 b are considered as fasting periodsensors as discussed above in the general discussion of the disclosure.Without excluding other types of sensors, sensor 4 a is in the followingexemplarily assumed as GPS sensor as an embodiment of a geolocationsensor, and sensor 4 b is assumed as a single or a plurality of contactsensors that are integrated in the diabetic's mattress. Sensors 4 a, 4b, may be operatively coupled to control unit 12 via any short rangecommunication link, e.g., Bluetooth or Bluetooth Low Energy, asdiscussed above in the context of CGM 2. In some embodiments, GPSreceiver 4 a may also be realized integral with infusion pump device 1or remote control unit 3. GPS receiver 4 a may also be integral with asmart phone or the like. Generally, GPS sensor 4 a may be integral withany device that is carried by the patient substantially continuously,such that the position of GPS sensor 4 a can be assumed to also indicatethe position of the diabetic.

Intervention unit 124 a of the embodiment shown in FIG. 4 may generallybe designed and operate similar to intervention unit 124 of thepreviously discussed embodiment, but differs with respect to thereceived control signal and its evaluation. Intervention unit 124 acombines the individual inputs that are received from clock unit 123, aswell as from sensors 4 a, 4 b, and evaluates them, in combination, ascontrol signal.

In an embodiment, inputs received from clock unit 123 and from sensors 4a, 4 b each define a binary input, with a combined input being given bya logic AND combination of the individual inputs. Intervention unit 124a may, for example, consider the beginning of a fasting period of thediabetic if the time of day is beyond a preset going-to-bed time (inputreceived from clock unit 123), the diabetic is in the bedroom (inputreceived from GPS sensor 4 a), and the diabetic's bed is weight-loadedto or beyond a given threshold (input received from contact sensor(s) 4b). With respect to the diabetic getting up, thereby indicating an endof the fasting period, a similar binary logic may be used. The diabeticmay, for example, be considered as having got up if the time of day isbeyond a preset getting-up time, his or her position is outside thebedroom and the mattress is not further loaded beyond the threshold.

The operational flow may generally be the same as shown in FIG. 3 asdiscussed above, with the deviating handling of the control signal beingreflected in step S4.

For both the embodiment of FIG. 1 as well as the embodiment of FIG. 4,additional user confirmations may be requested by the diabetic. That is,when the time of day and/or sensor signals indicate a beginning or anending of the fasting period, he or she may be requested confirm thisfact, and intervention unit 124 a may proceed with the following stepsonly if such confirmation is provided.

The variants and additions that may be made to the embodiment of FIG. 1may also be made to the embodiment of FIG. 4. Furthermore, only a singlefasting period sensor may be present or more that the above-mentionedtwo sensors 4 a, 4 b may be present and evaluated by intervention unit124 a. In a further somewhat less complex embodiment, sensors 4 a, 4 bare replaced by a “going to bed” button and a “getting up” button, asdiscussed above in context of the general disclosure. In a furthervariant, no control signal is provided to intervention unit 124 a fromclock unit 123, but control of the hypoglycaemia interventionexclusively relies on control signal as provided by sensors 4 a, 4 b. Itshall be noted that—in the ideal case of the diabetic following anidentical daily routine with little day-to-day variability anddisregarding the possibility of sensors 4 a/4 b providing wrong ormisleading signals as will be discussed below—the control signalprovided by clock unit 123 and by either of sensors 4 a, 4 b isredundant. Therefore, it is generally possible to only rely on either orboth of sensors 4 a, 4 b without evaluating the time of day.

In further embodiments, different logics may be used for the sensorevaluation. For example, the beginning of a fasting period may beassumed when indicated by at least two of the three criteria time ofday, GPS position and mattress load. Similarly, additional intelligencemay be added to the evaluation of sensors 4 a, 4 b. For example, anindication provided by either of sensors 4 a, 4 b, indicating thebeginning of a fasting period, is considered to be given if it occurs ator after the preset going-to-bed time but may be disregarded if alreadypresent for some time. For example, if GPS receiver 4 a is included in asmart phone, the diabetic may have placed or forgotten it on a bedsidecabinet during the day, resulting in GPS receiver 4 a wrongly indicatinga position in the bedroom. Similarly, a static load may be present onthe diabetic's bed or mattress, resulting in contact sensor(s) 4 bwrongly indicating the diabetic lying in bed. Additionally oralternatively, control unit 12 may consider the duration of anindication. For example, a diabetic may enter the bedroom and shortlysit down on his or her bed after the pre-set going to bed time, butwithout actually going to bed. Therefore, control unit 12 may consider acriterion that generally indicates the beginning of a fasting period tobe met only if sensors 4 a, 4 b provide corresponding and consistentinput for some preset minimum time period of, e.g., 15 minutes. Ananalogue approach may be used to prevent control unit 12 from mistakenlymisinterpreting a temporary nocturnal leaving the bed as terminating thefasting period and getting up.

In a further variant, sensors 4 a, 4 b are physical activity sensorsrather than fasting period sensors. Applying the same principals asdiscussed above in the context of fasting period sensors and using theoperational flow as shown in FIG. 3, intervention unit 124 a may in suchan embodiment be controlled in dependence of physical activity, inparticular sportive activity or exercise. In such an embodiment,operative coupling of intervention unit124 a and clock unit 123 may ormay not be present or may be configurable to be or not to be present.

In further variants, either or both of sensors 4 a, 4 b may serve asboth fasting period sensor and physical activity sensor. For example,sensor 4 a may be a GPS receiver that is exclusively used as fastingperiod sensor as discussed above. Sensor 4 b may be a pulse sensor,indicating the beginning of a fasting period if the pulse is below afirst threshold of, e.g., 70 beats per minute, and indicating sportiveactivity if the pulse is above a second threshold of, e.g., 130 beatsper minute.

While exemplary embodiments have been disclosed hereinabove, the presentinvention is not limited to the disclosed embodiments. Instead, thisapplication is intended to cover any variations, uses, or adaptations ofthis disclosure using its general principles. Further, this applicationis intended to cover such departures from the present disclosure as comewithin known or customary practice in the art to which this inventionpertains and which fall within the limits of the appended claims.

What is claimed is:
 1. A system for an electronically controlled pumpunit, comprising: a preset infusion schedule configured to control apump unit to infuse insulin into a diabetic's body in a substantiallycontinuous manner; an intervention unit configured to continuouslyevaluate a glucose indicative input from a glucose sensor for detectingan actual or expected hypoglycaemia and to execute, in response to anactual or expected hypoglycaemia, a temporary hypoglycaemiaintervention, the hypoglycaemia intervention including, for anintervention time interval, overriding the preset infusion schedule bytemporarily suspending insulin infusion or temporarily reducing insulininfusion below the preset infusion schedule; a control unit configuredto operatively coupled to a fasting period sensor and further configuredto generate a control signal according to a fasting period measureprovided by the fasting period sensor; and wherein the control unit isconfigured to enable execution of the hypoglycaemia intervention uponthe fasting period measure indicating that a diabetic associated withthe control unit has fallen asleep, has gone to bed, or can be expectedto fall asleep or go to bed soon.
 2. The system according to claim 1,wherein the intervention unit is configured to execute the hypoglycaemiaintervention upon a glucose value of the diabetic falling below a lowerintervention threshold.
 3. The system according to claim 1, wherein theintervention unit is configured to terminate the hypoglycaemiaintervention within a given time interval after starting thehypoglycaemia intervention, or upon a glucose value of the diabeticrising above an upper intervention threshold, or upon a resuming commandprovided by a user.
 4. The system according to claim 1, wherein thecontrol signal includes at least one of a lower intervention threshold,an upper intervention threshold, the reduction of insulin infusion belowthe preset infusion schedule, and the intervention time interval.
 5. Thesystem according to claim 1, wherein the control unit is configured tooperatively couple to a physical activity sensor and is configured togenerate a second control signal according to the physical activity ofthe diabetic, the physical activity sensor comprising one or more of anaccelerometer, a pedometer, or a pulse meter, an oxymeter, a breathsensor, body temperature sensors, heart rate sensor, ventilation ratesensor, amount of sweat and blood oxygen saturation sensor, EEG sensorsand an ECG sensor.
 6. The system according to claim 1, wherein theintervention unit is configured to execute, in case of an actual orexpected hypoglycaemia of the diabetic, alternative hypoglycaemiahandling routines, one of said alternative hypoglycaemia handlingroutines including executing the hypoglycaemia intervention.
 7. Thesystem according to claim 1, wherein the control unit is configured todetermine an overshot bolus and a compensation rate based on an amountof insulin that would be infused in accordance with the preset schedulewithin a compensation time interval following the hypoglycaemiaintervention.
 8. The system according to claim 1, wherein theintervention unit is configured to adapt its way of operation duringexecution of the hypoglycaemia intervention.
 9. The system according toclaim 1, wherein the intervention unit is configured, when executing thehypoglycaemia intervention, to successively reduce insulin infusionand/or, when terminating the hypoglycaemia intervention, to successivelyresume insulin infusion back to the preset schedule.
 10. The systemaccording to claim 1, wherein the intervention unit is configured todetermine a level of reduction of insulin infusion below the presetschedule in dependence of the glucose indicative input.
 11. The systemaccording to claim 1, wherein the control unit is configured toautomatically generate the control signal for the pump unit based oninput from the fasting period sensor.
 12. A diabetes therapy system,comprising: a pump unit configured to be carried by a diabetic; and acontrol unit operatively coupled to the pump unit and configured tocontrol operation of the pump unit, the control unit comprising: apreset infusion schedule configured to control the pump unit to infuseinsulin into a diabetic's body in a substantially continuous manner; anintervention unit configured to continuously evaluate a glucoseindicative input from a glucose sensor for detecting an actual orexpected hypoglycaemia and to execute, in response to an actual orexpected hypoglycaemia, a temporary hypoglycaemia intervention, thehypoglycaemia intervention including, for an intervention time interval,overriding the preset infusion schedule by temporarily suspendinginsulin infusion or temporarily reducing insulin infusion below thepreset infusion schedule; wherein the control unit is configured tooperative couple to a fasting period sensor and is further configured togenerate a control signal according to a fasting period measure providedby the fasting period sensor; and wherein the control unit is configuredto enable execution of the hypoglycaemia intervention upon the fastingperiod measure indicating that a diabetic associated with the controlunit has fallen asleep, has gone to bed, or can be expected to fallasleep or go to bed soon.
 13. The diabetes therapy system according toclaim 12, wherein the glucose sensor comprises a continuous glucosemonitor.
 14. The diabetic therapy system in accordance with claim 12,wherein the control unit is configured to automatically generate thecontrol signal for the pump unit based on input from the fasting periodsensor.